Colotta F, Borré A, Wang J M, Tattanelli M, Maddalena F, Polentarutti N, Peri G, Mantovani A
Centro Catullo e Daniela Borgomainerio, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
J Immunol. 1992 Feb 1;148(3):760-5.
The present study was designed to investigate the capacity of human mononuclear phagocytes to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein (MCP), alternative acronyms JE, monocyte chemotactic and activating factor, MCP-1, and tumor-derived chemotactic factor). Human PBMC exposed in vitro to bacterial LPS expressed high levels of MCP transcripts. Monocyte-depleted lymphoid cells were not induced to express MCP by LPS. Percoll-gradient purified monocytes were able to express high levels of MCP transcripts. In an effort to exclude a role of contaminating non-monocytic cells, mononuclear phagocytes were separated by flow cytometry and sorting: CD14+ cells exposed to LPS showed high levels of MCP mRNA. LPS-stimulated monocytes released chemotactic activity for monocytes that could be inhibited by absorption with anti-MCP antibodies. IL-1, TNF, IFN-gamma, granulocyte-macrophage-CSF and, to a lesser extent, macrophage-CSF, as well as inactivated streptococci, also induced MCP gene expression. Actinomycin D experiments indicated that induction of MCP in monocytes was gene transcription-dependent. The protein synthesis inhibitor cycloheximide (Cy) blocked IL-1-, TNF-, or LPS-induced MCP gene expression in monocytes. In contrast, expression of the structurally related chemotactic cytokine IL-8 was superinduced by Cy. Moreover, Cy superinduced MCP gene expression in cells other than monocytes, including endothelial cells, smooth muscle cell and fibrosarcoma cells, indicating different mechanisms of regulation in mononuclear phagocytes vs cells of other lineages. The capacity of cells of the monocyte-macrophage lineage to produce a cytokine that recruits and activates circulating monocytes may be of considerable importance in inflammatory and immunologic reactions. Thus, the mononuclear phagocyte system can autonomously regulate the extravasation and activation of immature elements of the same lineage, a key event in inflammation and immunity.
本研究旨在调查人类单核吞噬细胞产生对单核细胞具有趋化作用的细胞因子（单核细胞趋化蛋白（MCP），别名JE、单核细胞趋化和激活因子、MCP-1以及肿瘤衍生趋化因子）的能力。体外暴露于细菌脂多糖（LPS）的人外周血单核细胞（PBMC）表达高水平的MCP转录本。去除单核细胞的淋巴细胞不会被LPS诱导表达MCP。经Percoll梯度纯化的单核细胞能够表达高水平的MCP转录本。为了排除污染的非单核细胞的作用，通过流式细胞术和分选分离单核吞噬细胞：暴露于LPS的CD14+细胞显示高水平的MCP mRNA。LPS刺激的单核细胞释放对单核细胞具有趋化活性的物质，该活性可被抗MCP抗体吸收所抑制。白细胞介素-1（IL-1）、肿瘤坏死因子（TNF）、干扰素-γ（IFN-γ）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）以及在较小程度上的巨噬细胞集落刺激因子（M-CSF），还有灭活的链球菌，也诱导MCP基因表达。放线菌素D实验表明单核细胞中MCP的诱导是基因转录依赖性的。蛋白质合成抑制剂环己酰亚胺（Cy）阻断IL-1、TNF或LPS诱导的单核细胞中MCP基因表达。相反，结构相关的趋化细胞因子IL-8的表达被Cy超诱导。此外，Cy在单核细胞以外的细胞（包括内皮细胞、平滑肌细胞和成纤维肉瘤细胞）中超诱导MCP基因表达，表明单核吞噬细胞与其他谱系细胞的调节机制不同。单核巨噬细胞谱系的细胞产生募集和激活循环单核细胞的细胞因子的能力在炎症和免疫反应中可能相当重要。因此，单核吞噬细胞系统可以自主调节同一谱系未成熟细胞的外渗和激活，这是炎症和免疫中的关键事件。
